title: Postoperative intravenous infusion of donor-derived transplant acceptance-inducing cells as an adjunct immunosuppressive therapy in a porcine pulmonary allograft model.
abstract: There is very limited published information testifying to the safety and possible complications of cell-based therapies. Accurately assessing the potential risks of translating novel, cell-based immunosuppressive protocols into clinical trials is therefore extremely difficult. This report describes the use of a pulmonary allograft model in outbred miniature pigs as a preliminary step in the development of a safe, clinically feasible, cell-based immunosuppressive protocol. Single lung transplants were performed in 22 MHC Class I-mismatched donor-recipient pairs, which were randomized between four treatment groups. For the first 28 days postoperatively, all animals were immunosuppressed with methylprednisilone and tacrolimus, with or without preoperative irradiation; subsequently, pharmacological immunosuppression was stopped in all treatment groups. Animals in two groups also received a central venous infusion of donor-derived 'transplant acceptance-inducing cells' (TAICs) on the seventh and 14th days postoperatively. Allograft survival was monitored by sequential chest X-rays, bronchoscopies and transbronchial biopsy histologies. No acute adverse events were associated with the administration of TAICs and there was no evidence of accelerated graft rejection. The observations presented in this report represent an important first step towards the development of a clinically applicable protocol for the use of TAIC therapy in lung transplantation.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Warnecke
authors.forename: James A
authors.initials: JA
authors.lastname: Hutchinson
authors.forename: Paloma
authors.initials: P
authors.lastname: Riquelme
authors.forename: Bianca
authors.initials: B
authors.lastname: Kruse
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thissen
authors.forename: Murat
authors.initials: M
authors.lastname: Avsar
authors.forename: Gregor
authors.initials: G
authors.lastname: Zehle
authors.forename: Thomas
authors.initials: T
authors.lastname: Steinkamp
authors.forename: Carsten
authors.initials: C
authors.lastname: Peters
authors.forename: Rolf
authors.initials: R
authors.lastname: Baumann
authors.forename: Felix
authors.initials: F
authors.lastname: Gövert
authors.forename: Hendrik
authors.initials: H
authors.lastname: Ungefroren
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: André R
authors.initials: AR
authors.lastname: Simon
authors.forename: Johann H
authors.initials: JH
authors.lastname: Karstens
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Fred
authors.initials: F
authors.lastname: Fändrich
authors.forename: Martin
authors.initials: M
authors.lastname: Strüber
mesh_terms: D000208:Acute Disease; D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D006085:Graft Survival / Q000276:immunology; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007262:Infusions, Intravenous; D016040:Lung Transplantation; D008264:Macrophages / Q000276:immunology; D008775:Methylprednisolone / Q000494:pharmacology; D011182:Postoperative Care; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone